Plague is one of the most deadly infectious diseases on the planet, yet there is currently no available vaccine against Yersinia pestis approved for human use. Development of vaccines against the plague is especially important, because Y. pestis has the potential to be used as a bioterrorist weapon. Y. pestis is highly virulent, requiring only a small number of bacteria to initiate host infection (Titball et al., 1997). Although killed whole cell and attenuated live plague vaccines have been used in the past, the current focus of vaccine development against Y. pestis has shifted toward protein subunit vaccines, mainly because of cost and safety concerns.
Some of the most promising experimental protein subunits for use as subunit vaccines have been the F1 capsular antigen and the V antigen (LcrV), either used separately or as part of recombinant fusion proteins. However, acapsular, virulent strains of Y. pestis have been isolated. These spontaneous strains, without the F1 capsule, could evade immunity induced by F1 vaccinations. In such cases, a vaccine against F1 alone would not be effective. LcrV is another potential target for experimental vaccination protocols because of its important role in regulation of the Type III secretion system and its critical role in delivery of virulence proteins into the host eukaryotic cell. LcrV, in combination with F1 antigen, has been found to be protective against both bubonic and pneumonic plague. (Titball and Williamson, 2001). However, LcrV is known to have potent immunomodulatory effects that may not be desirable in a vaccine against Y. pestis, in that it may cause immunosuppression. Furthermore, LcrV exhibits serologic diversity, limiting the use of an LcrV vaccine produced against Y. pestis for protection against other Yersinia species.
The type III secretion apparatus is a conserved virulence mechanism required for virulence of Y. pestis. (Perry and Fetherson 1999). The type III secretion needle protein YscF has been suggested as an effective antigen for immunizing against Yersinia pathogens. See, e.g., U.S. Pat. Nos. 7,344,718 and 7,608,266 to Nilles, et al., the contents of which are incorporated herein by this reference. YscF protein is a surface-localized protein required both to secrete Yops, and to translocate toxins into the eukaryotic target cell. (Hoiczyk and Blobel, 2001).